The proposed research is aimed at characterizing and investigating the cellular physiology of the human peripheral blood lymphocyte in order to determine the role of various regulatory mechanisms in cell activation. We shall investigate the molecular basis for regulation of intracellular pH, determine the effect of mitogens on this regulation, and examine the ability of mitogen-stimulated lymphocytes, at various stages of activation, to volume regulate in response to hypotonicity. In addition, ionic modulation of cell contents, cell membrane, cell volume, T-cell receptor expression and growth factor production, and stimulated proliferation will be evaluated in both normal and mitogen-treated lymphocytes. These studies will thus provide a greater understanding of the fundamental molecular mechanisms of lymphocyte homeostasis and blastogenesis.